CATEGORY: diets/ketogenic
TECHNICAL: ***
SUMMARY:
This document is part one of a lengthy technical document
on Cyclical Ketogenic Diets (CKD's). It was written by a friend
of mine who, at the time, was a member on
another mailing list of people (mostly athletes) who used CKD's
for fat-loss, or to increase muscle gain in the gym.
This work is sort of like a treatise on the whole topic
of CKD's. It discusses what ketones are, what ketosis is, and the
effects that they have on your body. It's a fairly technical
document but a good read none the less.
If you read through it, you'll get an overall picture of
how your hormones respond to low-carb diets, and why low-carb diets
aid in fat loss. He's also very complete, and gives both positives
and negatives (as he sees them).
Bear in mind, though, that there have since been many
new studies that prove the efficacy of ketogenic diets. I just
wanted to show you this because it sort of lays it out in a fairly
easy to understand manner. I don't exactly agree with everything
he states here, but the jist is on target.

-------------------------------------------------------------
Surviving and Thriving on a Low Carb Diet
Beyond Atkins, Di Pasquale and Duchaine

by David Greenwalt B.Sc.

There is currently a great debate over which diet is best with
special emphasis on high fat/low carb or high carb/low fat. Each group
makes "spot" claims and neither really covers the issues which really
matter. What are these issues?

1. What is your goal? A. Fat loss? B. Muscle hypertrophy? C. Endurance
improvements? D. Longevity?

2. What foods do you like? A. Are you a vegetarian? B. Do you rarely eat
fresh fruits and vegetables? C. Do you like fish? D. Do you like to cook?
E. Are you married or single and does your spouse like to cook?

3. Do you plan on staying on this diet forever?

4. Are you going to use the diet temporarily for any number of reasons?

Many of the arguments which begin between rigid dieting rivals are
ghost-like, in that neither side knows, or cares, what the goals are of
the other. I, speaking personally, do not know a very large, muscular
vegetarian. An argument can be made that vegetarianism is healthiest,
however, from purely an observational perspective, I don't want to look
like any vegetarian I know or have ever seen. My goals, as a bodybuilder,
are to be as big and lean as I can be genetically and naturally. At this
point, a vegetarian and I are most likely polar opposites.

We must define our goals if we are to intelligently discuss diets
because simply talking about calories in, calories out or arguing over
diets which are supported in scientific literature as health-giving versus
diets purported to be more anabolic is assanine. It's almost like saying
"I like apples. Well, I like Ferrari automobiles." One has little to do
with the other.

There are so many diets for sale it can be bewildering to most
people. While all of these diets cause dietitians to shake their heads in
most cases, the personal bioindividuality isn't taken into consideration.
Take a recent example in which a relative of mine was counseled on a
weight problem by a physician (M.D.). My relative was told to eat low fat,
high carb, fruits and veges and eat fish at least twice a week because of
the benefits of the essential fatty acids in the fish. This advice is
patented medical standard protocol for anyone overweight and might be very
good for a majority of the population. Problem: My relative hates fish and
so do I for that matter. It is because of our individual likes and
dislikes that so many diets are made available. Most are effective in
their own right but many are imbalanced and do not include a wide variety
of foods. The Registered Dietitians (RD) of America push the Food Guide
Pyramid. The Atkins followers push the low carbohydrate diet. Others push
high protein or low protein, fasting, grapefruit only, soup only, no
fruits, etc. etc.. All may serve a purpose and all may be valid but until
we know about goals and individual sensitivities like intolerance to
certain foods, allergies, medical conditions and personal likes and
dislikes, there can be no intelligent discussion about which diet is
better.

This paper is an attempt to clear up the disinformation which exists
regarding the low carbohydrate diet which causes ketonuria and ketonemia.
Whether we're talking about an Atkins (low carb everyday) or Di Pasquale
(low carb 5 1/2 days, med. carb 1 1/2 days) they both cause considerable
ketosis.

There are those who follow a low carb diet and have done so for more
than a year. Atkins' book gives several examples of individuals who have
chosen to make low carb a part of their life style (5). A certain, small
percentage of epileptic children who suffer from intractable seizures and
don't respond well to drug therapy are purposely placed and medically
supervised on a low carb (herein called Ketogenic Diet) for periods of two
years or more (1). A key difference between an epileptic child and a
healthy bodybuilder consuming similar foods is fluid intake. A ketogenic
diet is closely monitored for an epileptic child because water intake is
restricted. This is because the ketone bodies, which are synthesized in
high quantities on a ketogenic diet, are actually the medicine for the
child. Epileptic children wouldn't respond as well if the "medicine" was
being flushed down the toilet in large quantities as the kidneys filtered
them with super consumption of water.

A non-epileptic, otherwise healthy adult does not have the same goal
as the epileptic child. Ketones are not medicine. They are an energy
source but not medicine to the healthy bodybuilder. They are a byproduct
of the diet which we want to excrete if in excess (We'll cover some
biochemistry later).

There are those who believe that the world nearly stops when benign
dietary ketosis is caused with a ketogenic diet. Scare tactics such as
"The Kreb's cycle collapses due to insufficient carbohydrate intake",
there will be more "bruising" of blood vessels because of higher fat
traffic on a ketogenic diet, increased risks of morbid obesity and
increased coronary heart disease lipid factors, and finally the great myth
that we must have hundreds of grams of carbohydrates per day to fuel the
brain and other tissues which require glucose for energy. Some of these
claims are simply false and others are completely unsubstantiated in
current medical journals. What must be taken into consideration, before
wild claims are made, are the ratios of the nutrients consumed and making
sure that whether it's an epidemiological study or small 10 person study,
were the study participants consuming a diet which is the same as those
following a typical ketogenic diet consisting of 70% fat, 20% protein and
5% carbohydrate? In nearly any case which examines fat intake and
increased risks of CHD and obesity, the fat intake is coupled, arm-in-arm
with high dietary carbohydrate ingestion or at least substantially higher
than the ketogenic 5% we're discussing in this paper.

The scare tactics, like the ones above, are used by the ill-advised
and ignorant who feel their diet is best. There is no cookie cutter
"best". There is no "one size fits all." For these reasons we can only
discuss physiology, biochemistry and scientific literature reviews which
are pertinent to humans following identical diets. Rat studies may be
better than nothing but not much better. In-vitro studies are only a place
for scientists to start, not a place for pragmatists to review.

In this paper I'll cover how a ketogenic diet works to support life
and activity and I'll also discuss how a ketogenic diet may even be
beneficial for some individuals. The research I have conducted for this
paper has led me to recommend a ketogenic diet for the following
individuals under the following circumstances:

1). Medically supervised epileptic children who don't respond to standard
drug therapy;

2). Dieting bodybuilders in precontest dieting phases, up to 12 weeks in
duration;

3). Strength phase athletes who want to incorporate more meat without a
large weight increase or any weight increase;

4). Type II diabetics (non-insulin dependent) 6-12 weeks, with
carbohydrates brought back in slowly and in measured quantities;

5). Anyone, who is otherwise healthy, but overweight and not happy with
the mirror may want to consider giving this diet a try for 6-12 weeks then
bring back in carbohydrates slowly and in reduced/measured quantities.

Yes, every class is temporary and it is believed, by this writer,
that a low carbohydrate, non-ketogenic diet would be the goal, eventually,
for anyone following a current ketogenic diet because ketosis is not a
normal, everyday, physiological state and was not intended to be from a
physiology standpoint. With all of this said let's begin.

What is a ketogenic diet and why would anyone want to modify their
current eating regimen to adapt to and follow a ketogenic diet?

First, let me say that the ketogenic diet dates back to biblical
times and in more modern times of the 20th century, the ketogenic diet has
been studied extensively with more research warranted even so (1).

The word ketogenic reveals the basic identity of the metabolic
process in humans of ketone (keto) production (genic). So we've produced
ketones. What does this mean and how are ketones used as ready substrates
to fuel anabolic and catabolic reactions, or better stated, how are
ketones used to fuel metabolism?

Ketones are a byproduct of fatty acid catabolism and this process of
breaking down triglycerides into glycerol and fatty acids is known as
lipolysis. Lipolysis is a normal physiological event occurring at times
when the body is utilizing fat as a fuel source and thus, breaking down
stored triglycerides and mobilizing free fatty acids and glycerol for
further catabolism into our body's absolute source of energy, ATP.
Lipolysis is activated during normal calorie-restrictive dieting
conditions and partially explains the reason we lose body fat during
hypocaloric periods or when we've created a net calorie deficiency when
activity, such as exercise, coupled with our basal metabolic rate creates
a greater need for calories than we are providing through our diet.

Ketone production is an indicator that lipolysis has been activated
and you are now, at least partially, burning fats for fuel. A ketogenic
diet, as you might expect, is a diet which promotes lipolysis as a chief
energy source, in preference to dietary glucose, the principal
carbohydrate utilized by the body after breaking down polysaccharides into
the monosaccharide glucose.

If lipolysis is the goal of a ketogenic diet for otherwise healthy
individuals, what is the best way to accomplish this? To give ourselves a
reference point and provide the baseline for comparison, I present the
highly touted pyramid of healthy eating.

The food guide pyramid, as many of you have seen, is representative
of what mainstream dietetics in 1996 want the majority of the American
population to consume on a daily basis for health, vigor and longevity.
The base and foundation of the pyramid suggests 6-11 servings of bread,
cereal, rice and pasta with the following other food groups and servings
providing the remaining calories in a given day: vegetables 3-5 servings,
fruits 2-4 servings, milk, yogurt and cheese 2-3 servings, meat, poultry,
fish, dry beans, eggs and nuts 2-3 servings, and last but not least fats,
oils and sweets are to be used sparingly. Upon visual observation of the
actual pyramid represented you can see the food groups are arranged with
the foods which should be consumed in greater quantities at the bottom,
and which are representative of a strong, solid foundation on which to
build (2).

When you are eating a ketogenic diet we turn everything upside down,
except that turning the pyramid upside down only provides an unstable
pivot point which the pyramid couldn't possibly be supported by. What we
really must do to represent the ketogenic diet appropriately is move the
food groups and provide for a solid base, consisting of fats and oils as
the foundation to build upon.

With a ketogenic diet, fats and oils are indeed representative of the
greatest proportion of the macronutrient organic molecules; lipids,
proteins, carbohydrates and nucleic acids eaten on a daily basis.

There's a good chance, as you sit there right now that you're in a
serious state of denial and many walls have already been put up doubting
the efficacy of this diet. I mean, after all, isn't it fat that makes us
fat? How could we possibly even maintain our current weight, let alone
lose weight with a diet which works off a structure of fats first, protein
second and carbohydrates third? Fat has been portrayed as an evil villain.
I mean, remember the traditional pyramid? Fats and oils are to be used
sparingly! Fat-free this and fat-free that. It's all good. It's all O.K.
if it's fat-free. Not true and even potentially dangerous for some people
who don't metabolize sugars properly.

In spite of the plethora of enzymes and metabolites in each cell,
metabolism is not random. Rather, it is highly regulated. If each of the
possible metabolic reactions were to occur at a fixed rate all of the
time, organisms would be incapable of reacting to changes in their
environment. For example, the intake of energy may be sporadic (e.g.
meals), yet organisms expend energy continuously. Metabolism must
therefore be regulated so that an organism can respond efficiently to the
availability of energy or food. When there is no intake of food but a
continued need for energy expenditure, metabolic fuels are mobilized from
storage depots at a rate sufficient to supply cells with oxidizable
substrates. Humans, for example, can survive periods of starvation as long
as five to six weeks when provided with water. A very obese adult could
probably endure a fast of more than a year, but physiological damage and
even death could result from the accompanying extreme ketosis after this
amount of time (7) (Remember, we're not starving, we're eating everyday).
Keep in mind that any organism responds not only to external demands but
also to genetically programmed instructions. The responses of organisms to
changing demands may involve alterations in many pathways or only a few
and may occur on a time scale ranging from less than a second to hours or
longer. Briefly, and very simplified, this is what occurs when a normal,
otherwise healthy person eats a typical meal consisting of 55%
carbohydrates, 30% fats, 15% protein- in other words, the "ideal diet".
Lipids are catabolized into fatty acids, carbohydrates to monosaccharides
and proteins are broken down into amino acids. Absorption of
macromolecules is primarily achieved in the small intestine and the
macromolecules are used to fuel glycolysis, the kreb's cycle and the
electron transport system, with carbohydrates being burned preferentially
to fats and proteins as an energy source. As long as glucose is plentiful
and insulin is present, glucose fuels the human machine and fats are
burned primarily as a fuel source only when carbohydrates are insufficient
or the body perceives an insufficiency, as is the case in diabetes
mellitus.

A ketogenic diet has been compared to a fasting/starvation diet
because in many ways, the metabolic pathways responsible for energy
production are similar in both. There is one striking difference which
should be very obvious, however, between a fasting/starvation diet and the
diet presented here. FOOD! We are neither fasting nor starving with a
ketogenic diet and in fact we are consuming, in some degree, all three of
the major energy-producing organic macromolecules which are, once again,
lipids, proteins and carbohydrates. To better illustrate how the body
could possibly survive and even thrive on such a diet it should be
understood that individuals who may benefit the greatest from a diet of
this type are individuals who don't process sugars properly, as is the
case in Type II, Noninsulin dependent, Adult-Onset Diabetes, and
individuals who are at greater risk for coronary heart disease due to
complications associated with morbid obesity.

Briefly, Noninsulin dependent diabetes is usually associated with
obesity and insulin secretion may be normal. Circulating levels of insulin
may even be elevated, thus the problem is not a shortage of insulin, but
insulin resistance resulting from decreased sensitivity, poor
responsiveness, or both. Chronic hyperglycemia (high blood sugar) is the
result. A drop in insulin production is often observed in individuals as
time passes and currently there is strong evidence to support a tiring of
the pancreas from chronic insulin output. A drop in insulin production is
often observed in individuals with NIDDM as time passes. NIDDM affects
about 5% of the population or approximately 12,500,000 people nationwide.
Chronic hyperglycemia can lead to a number of complications including
cataracts, sclerotic lesions in blood vessel walls, and general ill health
associated with obesity The aim of all regimens for the management of
diabetes is control of blood glucose levels. Dietary modifications are
often sufficient to control NIDDM and this type of diabetes may even
disappear with moderate weight loss and a program of exercise (3).

If obesity begets NIDDM and NIDDM begets obesity then we can begin to
realize the seriousness which surrounds a diet which may help control
blood glucose levels and which promotes the dissolving of fat. The health
risks of overfatness are so many that it has been declared a disease:
obesity. Besides diabetes and hypertension, other risks threaten obese
adults. Among them are high blood lipids, cardiovascular disease, sleep
apnea, osteoarthritis, abdominal hernias, some cancers, varicose veins,
gout, gallbladder disease, respiratory problems, liver malfunction,
complications in pregnancy and surgery, flat feet and even a high accident
rate. Moreover, after the effects of diagnosed diseases are taken into
account, the risk of death from other causes remains twice as high for
people with lifelong obesity as for others. An estimated 25 percent of
U.S. adults are overweight to a degree that incurs such risks (2).

As I stated before, a ketogenic diet is compared to a fasting diet
because of similar metabolic reactions for utilizing fatty acids and
protein as principle energy substrates when glucose levels are low. So, in
very simplified form, this is what happens when we change from a typical
"fed state" in which carbohydrates are plentiful and the fasting or
ketogenic state in which carbohydrates are restricted.

In the absorptive phase, lasting from 2-4 hours after a meal, the
level of glucose in the blood rises. Glucose is rapidly taken up by the
liver, skeletal muscle and the brain. If the level of glucose in the blood
rises above the ability of the kidney to reabsorb filtered glucose, the
excess is lost to the urine, as is the case with hyperglycemia and
diabetes.

High blood glucose triggers the release of insulin, which has many
physiological effects including stimulation of glycolysis (utilization of
glucose to form 2 ATP and 2 pyruvic acid molecules), fatty acid synthesis
and protein synthesis as well as inhibition of glycogenolysis (breaking
down glycogen to glucose), gluconeogenesis (conversion of noncarbohydrate
sources to glucose), fatty acid oxidation (cleaving long chain fatty acids
2 carbons at a time into shorter fatty acids), ketogenesis (producing
ketones) and proteolysis (breaking down proteins). Glucagon, which acts
only on liver, has effects that are in general, opposite those of insulin.
Insulin levels are high in the fed state (a state generally associated
with food consumption containing carbohydrates); glucagon levels are high
in the fasted state (or states in which glucose levels are low such as the
ketogenic diet).

Lipids entering the body during the absorptive phase are packaged in
chylomicrons (a transporter for lipids). Triglycerides in chylomicrons are
delivered to peripheral tissues (peripheral tissues are defined as any
tissue which is not the liver, indicating the liver's central role in
metabolism and filtration of toxins). Triglycerides are hydrolyzed outside
the cell and fatty acids are taken up, esterified (relinked with glycerol)
and stored (3). Stored lipid represents the body's most plentiful source
of potential energy. Relative to other nutrients, the quantity of lipid
available for energy is almost unlimited. The actual lipid fuel reserves
in a typical young adult male amount to about 90,000 to 110,000 kcal
(23,800kJ) of energy. In contrast, the carbohydrate energy reserve is
about 2% of this total, or approximately 2000 kcal (8400kJ) (6).

Dietary amino acids arrive at the liver during the absorptive phase.
These amino acids are either catabolized, used for protein synthesis or
permitted to pass unaltered to peripheral tissues. Oxidation of the amino
acids in liver generates a large amount of ATP, much of which is
immediately consumed by the pathways of gluconeogenesis and urea
synthesis, which remove the carbon and ammonia, respectively, generated by
amino acid catabolism.

In the transition into early starvation or initial ketogenic dieting,
the absorption of dietary glucose slows, the levels of insulin drops and
the level of glucagon rises. The liver responds to the hormonal changes by
breaking down glycogen and releasing glucose. Low levels of insulin are
also accompanied by an increase in the rate of lipolysis in adipose tissue
and an increase in the release of free fatty acids into circulation.

In addition to gluconeogenesis there is another revelation that may
come as a shock to some of you. When choice is available, most tissues use
fatty acids as fuels before ketone bodies, and BOTH BEFORE GLUCOSE (3).
This means that glucose is used only when it is abundant and other fuels
are scarce. Fatty acids are used in preference to glucose even though the
concentration of circulating glucose is always much higher than the
concentration of free fatty acids. The glucose-fatty acid cycle, first
proposed by Philip Randle, explains how the preference for glucose or
fatty acids is determined by metabolic conditions. Operation of the
glucose-fatty acid cycle requires that low concentrations of glucose
correspond to greater fatty acid availability. As I've stated earlier, low
availability of glucose results in decreased levels of insulin. Less
insulin means that lipolysis inhibition in adipose tissue has been lifted
and the availability of free fatty acids rises. The glucose-fatty acid
cycle contributes to the maintenance of blood glucose levels by sparing
the oxidation of glucose in peripheral tissues. This pattern of fuel use
is usually observed only when the availability of glucose is low, such as
after liver glycogen stores are exhausted, but the cycle predicts that any
rise in the level of circulating fatty acids will decrease glucose use.
The glucose-fatty acid mechanism suppresses the use of glucose when fatty
acids are available; when glucose is low, insulin is low, release and
catabolism of fatty acids is high, and products of fatty acid catabolism
(NADH, acetyl CoA and citrate) inhibit glucose degradation and spare the
use of glucose.

Other cycles of metabolism which assist in sparing glucose when
glucose levels are low include the Cori cycle which regenerates ATP from
lactate produced in muscle tissue. The lactate generated is returned to
liver for conversion back to glucose. The glucose-alanine cycle
interconverts glucose to alanine in muscle and then back to glucose once
again in liver.

Amino acids are the major gluconeogenic precursors initially and one
key difference between starvation or fasting and an eucaloric ketogenic
diet is that during starvation the use of endogenous amino acids requires
degradation of body proteins and accompanying loss of protein function.
With a ketogenic diet copious amounts of dietary proteins are being
consumed everyday. As you will see, the body strives to maintain protein
homeostasis and particularly, the precious intracellular proteins. When
given the choice, it is the belief of this writer that the body will
utilize dietary proteins during this initial gluconeogenic activity,
although some body proteins may initially be sacrificed through the
actions of various hormones until adaptation has occurred.

Protein turnover is continuous and the two processes comprising
turnover, synthesis and degradation, approximately balance one another in
the healthy adult. Whole-body turnover in humans is correlated to ones'
metabolic mass. Daily turnover of protein is calculated to be
approximately 4.6g/kg body weight. For the average 70-kg male, turnover of
whole-body protein would approximate 320 g daily (7). Individual body
proteins, however, vary in their turnover rate; the half-life of a protein
can range from only a few minutes to several months. Furthermore, neither
the turnover rate of an individual protein nor that of total body protein
remains constant. The rate of synthesis and degradation can be influenced
by a variety of factors related to nutrition, including immediate food
intake, previous diet, and overall nutrition status. Some have postulated
that during a ketogenic diet we will continuously show accelerated
proteolysis of intracellular proteins and muscle for gluconeogenesis which
is the opposite of what any athletic individual wants to do. During the
initial stages of a ketogenic diet the catabolism of muscle tissue may
occur for a brief period until the body has adapted to the diet and the
use of fatty acids and ketones as primary fuel substrates. Protein
degradation rates decrease concurrently so that even in chronic
starvation, which the low carb diet is not, daily losses of nitrogen
become quite small. For example, a person fully adapted to starvation can
survive at a cost of 3 to 4 g of his or her body protein per day. This new
priority is justified by the vital physiological importance of body
proteins. Proteins that must obviously be conserved for life to continue
include antibodies, needed to fight infection, enzymes, which catalyze
life-sustaining reactions and hemoglobin for the transport of oxygen to
tissues. The protein sparing shift at this point is from gluconeogenesis
to lipolysis, as the fat stores, and if following a ketogenic diet,
dietary fats, become the major supplier of energy. This shift to fat
breakdown also releases a large amount of glycerol, which becomes the
major gluconeogenic precursor, rather than amino acids (7). The principal
mechanism of adjustment to starvation is a change in hormone balance.
Decreased insulin activity, coupled with increased synthesis of
counterregulatory hormones such as glucagon, epinephrine and
norepinephrine promotes fatty acid mobilization from adipose tissue,
production of ketones and the availability of amino acids for
gluconeogenesis. Initially, in starvation or fasting and possibly
preadjustment to a ketogenic diet, glucocorticoids are important in
gluconeogenesis because they promote catabolism of muscle protein to
provide substrates for gluconeogenesis. We must remember that proteolysis
of muscle tissue may occur on a ketogenic diet in the early preadjustment
stages, however, ketogenic dieters are not starving and the initial
increased catabolism of body proteins will not continue for longer than as
little as a few days or perhaps up to a few weeks. Ketogenic dieters are
still consuming lipids, proteins and carbohydrates on a daily basis and
are not starving. An increased adjustment to starvation (or a ketogenic
diet) is characterized by a decrease in the secretion of glucocorticoids,
however (7). As fasting or starvation (or a ketogenic diet) continues,
tissues continue to use fatty acids and glucose for energy, but also begin
to use ketones formed in the liver from fatty acid oxidation. A decrease
in protein catabolism and gluconeogenesis occurs concurrently with the
brain's and other tissues' adaptation to ketones as a source of energy.
Glutamine metabolism in the kidney increases as starvation continues and
acidosis occurs. Within the kidney, glutamine catabolism generates
ammonia, which serves to help correct the potential for acidosis (7). Once
again, a difference between the ketogenic diet and starvation is acidosis.
Acidosis is well regulated in individuals who are not starving and even in
those who are, however, a discussion of protein and amino acid turnover
should include renal glutamine metabolism which is also a regulator of
blood pH.

As carbohydrates continue to remain low and the body is forced to use
fatty acids, proteins and glycerol via gluconeogenesis for fuels, fatty
acids are converted to ketone bodies, which, unlike fatty acids, can cross
the blood-brain barrier and serve as fuel for the brain, further sparing
the use of glucose. Less use of glucose at this state means less

What we've clearly shown thus far, is that the body is adaptive and
utilizes many complex mechanisms to not only spare glucose for organs
which absolutely require it like the kidney medulla, the retina, red blood
cells and parts of the brain, but also regenerates necessary glucose from
non carbohydrate sources.

If further evidence is necessary to convince any doubters that a low
carbohydrate diet can not only sustain life but provide a great abundance
of energy for daily activities, exercise and even intense exercise, I'll
provide the following scenario:

In humans, in the fed state (which as I mentioned before is generally
associated with carbohydrate ingestion), the brain requires about 120
grams of glucose per day and all other glycolytic tissues require about 60
grams per day. Total glucose necessary per day during intermediate
starvation is reduced to approximately 110-120 grams per day (3). The
body, at this stage, is already making adjustments for reduced
carbohydrate availability. As ketone bodies become more readily available,
they can substitute as an energy source in tissues which would normally
otherwise utilize glucose as a fuel source. What tissues can utilize
ketone bodies for energy?

(1) The brain (2) Muscle (3) The Kidneys (4) Small intestine

The sparing effect of ketone bodies on glucose when a eucaloric diet
is still being utilized, ensures that peripheral tissues will have the
glucose they need to function efficiently. During intermediate starvation
and potentially, during initial ketogenic dieting, about 40-50 grams of
the 110-120 grams of glucose used per day are accounted for by the
activity of the Cori cycle (if you'll think back, the Cori cycle was a
cycle of glucose regeneration from glucose to lactate in muscle and then
back to glucose again in the liver). In starvation, lipolysis of adipose
tissue will contribute between 15 and 20 grams of glucose per day and
remains fairly constant during starvation. We can conclude that lipolysis
of adipose tissue as well as fatty acid oxidation of dietary lipids with a
ketogenic diet will produce glucose in at least as great a concentration
as starvation.

So far we've created approximately 70 grams of glucose via the Cori
cycle and lipolysis with another 40-50 grams of glucose needed to fill the
bank and provide peripheral tissues with glucose to operate effectively.
How do we get the remaining glucose we absolutely must have during
intermediate starvation or preadjustment ketogenic dieting?
Gluconeogenesis from amino acids is quite high, even in the absorptive
phase when carbohydrates are present. During starvation, proteolysis of
peripheral tissues increases to provide gluconeogenic precursors at the
liver. During the ketogenic diet protein is consumed in copious amounts,
thus thwarting the debilitating effects of losing precious cellular
proteins and muscle protein. The production of 100 grams of glucose
requires the breakdown of about 175 grams of amino acids. During
starvation this cannot last long as even a small amount of lost protein to
provide energy is accompanied by loss of functional capacity (3). Once
again, we're not starving, we're eating generous portions of lipids,
proteins and minimal carbohydrates. A typical 180 pound bodybuilder, for
instance, will consume approximately 180-360 grams of protein per day
depending on training philosophy and ideas about the benefits in general
of consuming additional protein as a bodybuilder. There is even stronger
evidence to suggest that endurance athletes may benefit from increased
protein consumption (even more so than bodybuilders) and they may in fact
be consuming large amounts of protein from their diet as well. I cannot
speak for them, however (4).

We've already exceeded the minimal necessary amounts of glucose to
keep peripheral tissues functioning efficiently and we haven't even eaten
any carbohydrates yet. Let's not forget that most ketogenic diets don't
advocate abstinence from carbohydrates completely and that most
bodybuilders or dieting individuals following a ketogenic diet will
consume between 30 and 50 grams of carbohydrates per day. We've already
shown that glucose will be plentiful and available to fuel tissues which
require it but let's review thus far how it was accomplished. (1) A
reduction in carbohydrate intake has reduced insulin production, although
insulin in normal, healthy individuals is present at all times in blood,
albeit, in lower concentrations during low carbohydrate ingestion. (2) A
lowering of insulin has lifted the inhibition on lipolysis and lipolysis
is now stimulated. If calories are insufficient to maintain BMR plus
activity then adipose tissue and dietary fatty acids will effectively be
used to generate energy via the beta oxidation of free fatty acids and
gluconeogenesis of glycerol, the back bone of stored triglycerides. In
either case, hypocaloric or eucaloric dieting, lipolysis will be enhanced
and the choice of fuels will be determined by calories consumed with
preference given to dietary lipids first and adipose tissue second. (3)
The glucose-fatty acid cycle dictates that when carbohydrate is low, fatty
acids can serve as a preferred fuel source, thus, lowering the need for
glucose. (4) The Cori cycle recycles glucose by converting glucose into
lactate within muscle and then a reconversion of lactate in the liver back
to glucose takes place, thus completing the cycle. (5) The glucose-Alanine
cycle is similar to the Cori cycle except that glucose is converted into
pyruvate within muscle once again and then to Alanine, also within muscle,
which is transported to the liver for reconversion into glucose. (6) The
body has adapted to the reduction in glucose and is ready and willing to
utilize ketone bodies as a fuel source in certain tissues. (7) We are
still eating some carbohydrates every day!

As starvation or the ketogenic diet continues, lipolysis continues to
release considerable amounts of fatty acids, which are taken up by the
liver. Fatty acids enter the mitochondria, where they are partially
oxidized. The citric acid cycle in liver can absorb only a fraction of the
acetyl CoA produced by beta oxidation, and most is converted to the ketone
bodies beta-hydroxybutyrate and acetoacetate. Ketone bodies that are taken
up and metabolized by tissues spare the use of glucose, just as glucose is
spared by the operation of the glucose-fatty acid cycle.

As ketone bodies initially become available, they provide up to 50%
of the energy requirement of skeletal muscle. The most important overall
effect, however, of the use of fatty acids and ketone bodies as
alternatives to glucose, is that, as I stated in previous pages, less
demand for glucose means that less proteolysis of muscle protein is
required to supply the gluconeogenic pathway. Ketone bodies are acidic,
water soluble short chain fats and if left to accumulate in an
uncontrolled fashion could have devastating effects on our central nervous
system. Excess ketones are filtered and diluted ( as they are water
soluble) and excreted in urine. Our body also has very capable buffering
systems in place, (one previously mentioned is the use of renal glutamine
metabolism to create ammonia) to accept the extra hydrogen ions released
in the blood which prevent wild fluctuations in blood pH.

An excellent example of buffer capacity is found in the blood plasma
of mammals, which has a remarkable constant pH of 7.4. Consider the
results of an experiment that compares the addition of an aliquot of
strong acid to a volume of blood plasma with a similar addition of either
physiological saline or water. When 1.0ml of 10 M HCL (hydrochloric acid)
is added to 1000ml of physiological saline or water that is initially at
pH 7.0, the pH is lowered to 2.0. However, when 1.0 ml of 10 M HCL is
added to 1000 ml of blood plasma at pH 7.4, the pH is again lowered, but
only to 7.2- impressive evidence for the effectiveness of physiological
buffering (3).

The pH of the blood is primarily regulated by the carbon
dioxide(CO2)-carbonic acid(H2CO3)-bicarbonate(HCO3) buffer system. The
buffer capacity of blood depends upon equilibria between gaseous carbon
dioxide(which is present in the air spaces of the lungs), aqueous carbon
dioxide(which is produced by respiring tissues and dissolved in blood),
carbonic acid, and bicarbonate. When the pH of blood falls due to a
metabolic process that produces excess hydrogen ions, the concentration of
carbonic acid increases momentarily, but carbonic acid rapidly loses water
to form dissolved carbon dioxide(aqueous), which enters the gaseous phase
in the lungs and is expired as carbon dioxide (gaseous). An increase in
the partial pressure of carbon dioxide in the air expired from the lungs
thus compensates for the increased hydrogen ions. This system of pH
regulation effectively neutralizes the excess hydrogen ions, however, it
does so at the cost of depleting the blood bicarbonate. A bicarbonate
repletion mechanism exists in the kidney and requires the amino acid
glutamine (3). Conversely, if the pH of the blood rises, the concentration
of bicarbonate increases transiently, but the pH is rapidly restored as
the breathing rate changes and the reservoir of carbon dioxide(gaseous) in
the lungs is converted to carbon dioxide (aqueous) and then to carbonic
acid in the capillaries of the lungs. Again, the equilibrium of the blood
buffer system is rapidly restored by changing the partial pressure of
carbon dioxide in the lungs (3).

One point which must be addressed when discussing the effects of
buffering systems and the acidic nature of ketone bodies is the
incorrectly assumed potential for ketoacidosis in individuals who still
have the ability to secrete normal amounts of insulin from the pancreas.
In diabetics, who are vivid negative examples of what can go wrong with
the integration of metabolism and metabolic regulation (homeostasis) for
the continuance of life, ketoacidosis and metabolic acidosis are very real
and serious problems which must be taken into consideration by those
individuals. In diabetics, who are already at risk for chronic
hyperglycemia, diuresis leads to a dehydration compounded by increased
insensible water loss due to hypernea of metabolic acidosis. Metabolic
acidosis results from the excessive ketogenesis occurring in the liver.
Peripheral circulatory failure, a consequence of severe hemoconcentration
leads to tissue hypoxia with a consequent shift of the tissues to
anaerobic metabolism. Anaerobic metabolism raises the concentration of
lactic acid in the blood, thereby worsening the metabolic acidosis. The
ketonuria along with glucosuria associated with acidosis causes an
excessive loss of sodium from the body; loss of this extracellular cation
further compromises body water balance. A net loss of potassium, the chief
intracellular cation, accompanies increased protein catabolism and
cellular dehydration, both of which characterize uncontrolled diabetes
(7).

In non-insulin dependent diabetics or the overweight but healthy
individuals who are utilizing a ketogenic diet this cascade of events,
which eventually may lead to coma or death, does not occur. If it did,
we'd have a lot of very sick or dead dieters to deal with and in all
actuality we wouldn't be writing this paper because the diet would not be
as "trendy" as it has become. Why then, don't type II diabetics or normal
but overweight individuals succumb to the hazards of ketoacidosis or
metabolic acidosis? The answer lies in the body's innate ability to
maintain homeostasis. With a ketogenic diet we are mobilizing large
amounts of free fatty acids which are producing ketone bodies in large
quantities. Ketone bodies are acidic. If we agree thus far in this
paragraph then let's elucidate the reason we aren't all dropping like
flies. When plasma ketone concentrations reach 4-6mmol, insulin release
from the pancreas is stimulated. This blunts (but does not normalize)
lipolytic activity in the fat cell such that plasma free fatty acid (FFA)
levels are fixed at about .7-1.0mmol - sufficient to allow moderate
production of aceto-acetate and 3-hydroxybutyrate by the liver, but
insufficient to allow maximum rates of production required to develop
ketoacidosis. In type I diabetics subjects the protective ketone-insulin
feedback loop cannot operate because of beta-cell failure in the Islets of
Langerhans. As a consequence, plasma FFA reach much higher concentrations,
driving ketone production to maximal rates, thereby leading to the
ketoacidotic state (8). Another, perhaps more obvious advantage, is our
ability as human beings to utilize common sense. Since the kidneys are
going to help us flush unused ketones then we can help our kidneys do
their job by drinking a lot of distilled water everyday. At least one
gallon of distilled water should be consumed everyday when individuals are
following a ketogenic diet or any diet for that matter.

I've spent a lot of time covering the basic metabolic pathways
associated with a ketogenic diet consisting of 75% lipids, 20% proteins
and 5% or less carbohydrate. There are those who profess to have all the
answers and shriek at a diet which promotes such a high fat consumption
and, in the beginning, nearly excludes certain food groups. There are
great differences between this type of diet and someone who is ill with
Insulin Dependent Diabetes Mellitus. A normal person produces insulin but
may not regulate blood glucose levels and uptake very efficiently due to
many factors. An Insulin Dependent Diabetic does not produce insulin, or
very much, and has lost much of the control that healthy, but overweight
individuals possess.

You may be curious about exactly what foods are acceptable for this
diet. In general: All meat, all fish, all fowl, all shellfish, all eggs,
almost all cheeses, vegetables of 10% carbohydrate or less, cauliflower,
tomatoes, spinach, sauerkraut, broccoli, brussels sprouts, spices, sugar
free beverages, fats and oils, nuts and seeds in moderation, peanut butter
in moderation and water as the principle dietary solvent (5).

Final recommendations and general guidelines for anyone following a
ketogenic diet: Generally speaking, when individuals are strictly
following the initial dieting changes which accompany this diet they are
lacking in various vitamins, minerals and fiber. While there is great
controversy over whether fiber is of vital importance for life-long health
and cancer prevention, this writer believes fiber should be sought and not
avoided. Because I have made initial recommendations that anyone following
this diet will not be on it in its strict form for more than 12 weeks
there are some simple ideas which I think are important; (1) Drink at
least one gallon of distilled water every day, (2) While carbohydrate
intake will most likely be limited to 30-50 grams per day it is important
to make the carbohydrates you do eat of a fibrous nature. Vegetables which
are high in fiber and nuts can help balance the carbohydrate/fiber issue.
They are also a rich source of vitamins and minerals. I suggest not eating
any carbohydrate that contains greater than a 3:1 ratio of carbs to fiber
grams. In other words, if the package of nuts you're eating has 6 grams of
carbs, it should also contain 2 grams of fiber or more. Assuming the eggs
and other products you're going to be eating that contain trace amounts of
carbs equals no more than 6 grams of carbs per day, you will have between
24 and 44 grams of carbs left to consume. In these carbs you should strive
to eat those which contain the 3:1 ratio of carbs to fiber. In this way
you'll get between 8 and 15 grams of fiber everyday. You may also want to
take a carbohydrate-free fiber supplement, available at any health food
store, if your fiber intake is less than the range above. Additionally, if
your bowel movements are less than one per day, after two weeks of
adaptation to the diet, you may want to consider adding in a fiber
supplement as well. (3) Take a complete multi-vitamin and mineral
supplement everyday to prevent any possibility of vitamin and mineral
deficiencies, (4) Optionally, take free-form glutamine in supplemental
form for optimal intestinal, skeletal muscle and renal functioning.

The walk-away message from this paper is an understanding that
lipolysis is the process of dissolving fat and there is "no lipolysis
without ketosis and no ketosis without lipolysis" (5) and how this diet
differs substantially from a starvation diet and doesn't cause metabolic
acidosis in normal insulin producing individuals. We aren't going to die
by placing our bodies in a state of benign dietary ketosis while we get
our blood sugar under control and lose excess weight in the process. In
fact, we may actually see an improvement in energy, health and mental
stability in the absence of wild fluctuations in blood sugar. Eventually,
you will want to bring in other food groups and carbohydrates, however, if
you're carbohydrate sensitive, you will want to bring them in slowly and
in measured quantities, not exceeding the carbohydrate levels which your
body can efficiently process without laying down fat and without causing
wild fluctuations in blood sugar. In the meantime, many people will enjoy
a reduction in bodyfat with an exceptionally little amount of lean mass
lost in the process, as well as an increase in perceived energy and
perhaps, for the first time in many years, a stabilization of blood sugar.

References:

1. Spalding, K, Amorde, MS RD, (J Am Diet Assoc, Nov. 96, pp.1134)

2. Cataldo, Debruyne, Whitney, "Nutrition and Diet Therapy", 1995

3. Moran, Scrimgeour, Horton, Ochs, Rawn "Biochemistry" 2nd Ed., 1994

4. Wolinsky, Ira, Hickson, James "Nutrition in Exercise and Sport", 2nd
Ed., 1994

5. Atkins, Robert MD "Dr. Atkins New Diet Revolution", 1995

6. Mcardle, Katch, Katch "Exercise Physiology", 1996

7. Groff, J, Sareen, G, Hunt, S "Advanced Nutrition and Human Metabolism",
2nd Ed, 1995

8. Rifkin, Porte "Diabetes Mellitus: Theory and Practice", 1990

MORE READING ON KETOGENIC DIETS

Wing RR; Vazquez JA; Ryan CM Cognitive effects of ketogenic
weight-reducing diets Int J Obes Relat Metab Disord, 19:11, 1995 Nov,
811-6

Gumbiner B, etal Effects of diet composition and ketosis on glycemia
during very-low-energy-diet therapy in obese patients with
non-insulin-dependent diabetes mellitus Am J Clin Nutr, 1996 Jan

Amari A, et al Achieving and maintaining compliance with the ketogenic
diet J Appl Behav Anal, 1995 Fall

Nebeling LC, et al Effects of a ketogenic diet on tumor metabolism and
nutritional status in pediatric oncology patients: two case reports. J Am
Coll Nutr, 1995 Apr

Nebeling LC, et al Implementing a ketogenic diet based on medium-chain
triglyceride oil in pediatric patients with cancer. J Am Diet Assoc, 1995
June

Baron JA, et al A randomized controlled trial of low carbohydrate and low
fat/high fiber diets for weight loss Am J Public Health, (1986 Nov)
76(11):1293-6

Alford BB et al The effects of variations in carbohydrate, protein, and
fat content of the diet upon weight loss, blood values, and nutrient
intake of adult obese women. J Am Diet Assoc (1990 Apr) 90(4):534-40

Rabast U, et al Loss of weight, sodium and water in obese persons
consuming a high or low carbohydrate diet. Ann Nutr Metab (1981)
25(6):341-9

Lambert EV, et al Enhanced endurance in trained cyclists during moderate
intensity exercise following 2 weeks adaptation to a high fat diet. Eur J
Appl Physiol (1994) 69(4):287-293

McCargar LJ, et al Dietary carbohydrate-to-fat ratio: Influence on
while-body nitrogen retention, substrate utilization, and hormone response
in healthy male subjects. Am J Clin Nutr (1989 Jun) 49(6):1169-78

Lopez A, et al Some interesting relationships between dietary
carbohydrates and serum cholesterol. Am J Clin Nutr (1966 Feb)
18(2):149-153

Kasper H, et al Letter: Behavior of body weight under a low carbohydrate,
high fat diet. Am J Clin Nutr (1975 Aug) 28(8): 800-1

Kasper H, et al Response of body weight to a low carbohydrate, high fat
diet in normal and obese subjects. Am J Clin Nutr (1973 Feb) 26(2):197-204

Young CM, et al Effect of body composition and other parameters in obese
young men of carbohydrate level of reduction diet. Am J clin Nutr (1971
Mar) 24(3):290-6

Hodges RE, et al Dietary carbohydrates and low cholesterol diets: effects
on serum lipids on man. Am J Clin Nutr (1967 Feb) 20(2):198-208

Krehl WA, et al Some metabolic changes induced by low carbohydrate diets.
Am J Clin Nutr (1967 Feb) 20(2):139-148

Rosen JC, et al Mood and appetite during minimal-carbohydrate and
carbohydrate-supplemented hypocaloric diets. Am J Clin Nutr (1985 Sep)
42(3):371-9

Tremblay A, et al Diet composition and postexercise energy balance Am J
Clin Nutr (1994 May) 59(5):975-9

Phinney SD, et al Capacity for moderate exercise in obese subjects after
adaptation to a hypocaloric, ketogenic diet. J Clin Invest (1980 Nov)
66(5):1152-61

Yang MU, et al Composition of weight lost during short-term weight
reduction. Metabolic responses of obese subject to starvation and
low-calorie ketogenic and nonketogenic diets. J Clin Invest (1976 Sep)
58(3):722-30

Council on Foods and Nutrition A critiquie of low-carbohydrate ketogenic
weight reduction regimens. A review of Dr. Atkins' diet revolution. JAMA
(1973 Jun 4) 224(10):1415-9

Vazquez JA, et al Protein sparing during treatment of obesity: ketogenic
versus nonketogenic very low calorie diet. Metabolism (1992 Apr)
41(4):406-14

Newbold HL Reducing the serum cholesterol level with a diet high in animal
fat. South Med J (1988 Jan) 81(1):61-3

Kuroshima A, et al Effect of a high-fat diet on metabolic responses to
exercise. Jpn J Physiol (1975) 25(5):575-84

Rabast U, et al Comparative studies in obese subjects fed
carbohydrate-restricted and high carbohydrate 1,000 calorie formula diets.
Nutr Metab (1978) 22(5):269-77

Golay A, et al Similar weight loss with low or high carbohydrate diets. Am
J Clin Nutr (1996 Feb) 63(2):174-8

Kundu SK, Judilla Am Novel solid-phase assay of ketone bodies in urine.
Clin Chem (1991 Sep) 37(9):1565-9

Fery F, et al Hormonal and metabolic changes induced by an isocaloric
isoproteinic ketogenic diet in healthy subjects. Diabete Metab (1982 Dec)
8(4):299-305

Kather H, et al Influences of variation in total energy intake and dietary
consumption on regulation of fat cell lipolysis in ideal weight subjects.
J Clin Invest (1987) 80(2):556-72

Giorski J. Muscle triglyceride metabolism during exercise. Can J Phys
Pharm (1992) 70(1):123-31

Symons JD, et al High-intensity exercise performance is not impaired by
low intramuscular glycogen. Med Sci Sports Exerc (1989) 21(5):550-7

Evans WJ, et al Dietary carbohydrates and endurance exercise. Am J Clin
Nutr (1985) 41(5):1146-54

Mitchell GA, et al Medical aspects of ketone body metabolism. Clin Invest
Med (1995) 18(3):193-216 Rabast U, et al Dietetic treatment of obesity
with low and high carbohydrate diets. Intl J Obesity (1979) 3(3):201-211

Liu VJ, et al Chromium and insulin in young subjects with normal glucose
tolerance. Am J Clin Nutr (1982) 25(4):661-67

Rickman F, et al Changes in serum cholesterol during the Stillman diet.
JAMA (1974) 228:54

Fontbonne A, et al Coronary heart disease mortality risk: plasma insulin
level is a more sensitive marker than hypertension or abnormal glucose
tolerance in overweight males: the Paris prospective study. Intl J Obesity
(1988) 12:557-65

Coulston AM, et al Deleterious metabolic effects of high-carbohydrate,
sucrose-containing diets in patients with non-insulin dependent diabetes
mellitus. Am J Med (1987) 82:213-20

Coulston AM, et al Original articles: persistence of hypertriglyceridemic
effect of low-fat high-carbohydrate diets in NIDDM patients Diabetes Care
1989 12(2):94-101

Stout, RW. Hyperinsulinaemia- a possible risk factor for cardiovascular
disease in diabetes mellitus. Horm Met Res (1985) 15:37-41

Tremblay A, et al Nutritional determinants of the increase in energy
intake associated with a high-fat diet Am J Clin Nutr (1991) 53:1134-37

McGill HC The relationship of dietary cholesterol to serum cholesterol
concentration and to atherosclerosis in man. Am J Clin Nutr (1979)
32:2664-2702

Willett WC, et al Relation of meat, fat and fiber to the risk of colon
cancer in a prospective study among women. NEJM (1990) 323(24):1664-72

Willett WC, et al Original article: dietary fat and the risk of breast
cancer. NEJM (1987) 316(1):22-28 Macquart-Moulin G, et al Case control
study on colorectal cancer and diet in Marseilles. Intl J Cancer (1986)
38(2):183-91

Haenszel W, et al A case-control study of large bowel cancer in Japan. J
National Cancer Institute (1980) 64(1):17-22

Tuyns AJ, et al Colorectal cancer and the intake of nutrients:
oligosaccarides are a risk factor, fats are not. A case-control study in
Belgium. Nutrition and Cancer (1987) 10(4):181-96

:cool: TJ :cool: